RPEP-08204 · 2024A 56-year-old woman with a pancreatic neuroendocrine tumor (pNET) developed severe hypercalcemia caused by tumor secretion of PTHrP — a complication reported in only 1.1% of pNET cases.
Despite treatment with IV fluids, bisphosphonates, calcitonin, and denosumab (a RANKL inhibitor), hypercalcemia recurred repeatedly. Adjunctive somatostatin analog therapy also failed to control calcium levels. The patient was not a candidate for curative surgery (cytoreduction). She died from refractory hypercalcemia — the metabolic complication, not the tumor itself, was the cause of death.
Foley, Erin; Hari Dass, Prashanth; O'Sullivan, Esther ·
RPEP-08209 · 2024Fmoc-diphenylalanine (Fmoc-FF) peptides self-assembled into hydrogels with nanofiber morphology and compressive moduli of 174-277 Pa, mimicking features of the natural extracellular matrix. Three solvent systems were tested: DMSO, HFP, and deionized water.
Human mesenchymal stem cells (MSCs) encapsulated in the peptide hydrogels and subjected to mechanical stretching exhibited elongated morphology with distinct microfilament fibers, compared to control cells that remained round and spherical. Peptide gels at 5 mM concentration maintained 100% MSC viability. The Fmoc-FF/HFP and Fmoc-FF/DMSO preparations produced the best results for cell alignment after stretching.
Fouladgar, Farzaneh; Zadeh Moslabeh, Forough Ghasem; Kasani, Yashesh Varun; Rogozinski, Nick; Torres, Marc; Ecker, Melanie; Yang, Huaxiao; Yang, Yong; Habibi, Neda ·
RPEP-08211 · 2024Tirzepatide (Mounjaro), the first dual GIP/GLP-1 receptor agonist, demonstrated superiority over multiple established diabetes treatments in the phase III SURPASS clinical trial program. Given once weekly by subcutaneous injection, tirzepatide outperformed dulaglutide 0.75 mg, semaglutide 1 mg, and both basal and prandial insulin for both blood sugar control and weight loss in adults with inadequately controlled type 2 diabetes.
The drug showed a favorable safety profile consistent with GLP-1 receptor agonists, with a low risk of clinically significant hypoglycemia and no increased risk of major adverse cardiovascular events. The most common side effects were gastrointestinal — nausea, diarrhea, decreased appetite, and vomiting — and were mostly mild to moderate.
France, Nicole L; Syed, Yahiya Y · Review
RPEP-08212 · 2024All eight included studies uniformly reported reductions in weight and BMI among PCOS patients prescribed GLP-1 RAs (liraglutide or exenatide). Additional benefits included improvements in anthropometric parameters (waist circumference, total fat percentage), glucose homeostasis, cardiovascular inflammatory markers (MR-proANP and MR-proADM), rates of natural pregnancy, and menstrual regulation.
However, findings regarding lipid profile effects were inconsistent across studies. Short-term adverse effects were noted but long-term effects remain undetermined. The studies showed wide geographic diversity, suggesting benefits across racial and ethnic backgrounds.
Frangie Machado, Melissa; Shunk, Taylor; Hansen, Grace; Harvey, Charles; Fulford, Baylee; Hauf, Shane; Schuh, Olivia; Kaldas, Matthew; Arcaroli, Elena; Ortiz, Justin; De Gaetano, Joseph ·
RPEP-08214 · 2024From 64 clinical studies on clozapine (2012-2022), key findings included:
- No investigated drug was superior to clozapine for schizophrenia treatment
- Clozapine was superior to olanzapine and risperidone for aggression and depression reduction
- Metabolic parameters changed comparably between clozapine and olanzapine after 8 years
- Eight drugs identified as potentially effective for clozapine-induced weight gain, including the GLP-1 receptor agonists liraglutide and exenatide, alongside metformin and orlistat
- Scopolamine, atropine drops, and metoclopramide were effective for clozapine-induced hypersalivation
- Ziprasidone, haloperidol, and aripiprazole showed positive augmentation effects when added to clozapine
Freibüchler, Anton; Seifert, Roland ·
RPEP-08215 · 2024In this post hoc analysis of the SURPASS-2 trial, tirzepatide at all three doses (5, 10, and 15 mg) outperformed semaglutide 1 mg in improving both pancreatic beta-cell function and insulin sensitivity in people with type 2 diabetes over 40 weeks.
Tirzepatide improved HOMA2-B (beta-cell function) by 96.9–120.4% compared to 84.0% with semaglutide (p<0.05). Insulin resistance (HOMA2-IR) decreased by 15.5–24.0% with tirzepatide versus only 5.1% with semaglutide (p<0.05). Tirzepatide 10 and 15 mg also significantly reduced fasting C-peptide (5.2–6.0%) and fasting glucagon (53.0–55.3%) compared to semaglutide. These advantages in HbA1c and weight loss held across all baseline quartiles of beta-cell function and insulin resistance.
Frias, Juan P; De Block, Christophe; Brown, Katelyn; Wang, Hui; Thomas, Melissa K; Zeytinoglu, Meltem; Maldonado, Juan M · Rct Post Hoc
RPEP-08231 · 2024In a 34-year-old woman with 23 years of type 1 diabetes, adding semaglutide (1 mg weekly) to insulin therapy produced dramatic improvements in just 2 months: 12 kg weight loss (63→51 kg), 15% reduction in body fat percentage, 7% decrease in visceral fat, reduced HbA1c (from 8.3%), lower insulin doses, and decreased glycemic variability.
Gad, Hoda; Malik, Rayaz A ·
RPEP-08240 · 2024A new fluorine-18-labeled somatostatin analog ([Al18F]NODA-MPAA-HTA) was synthesized with 60–80% radiochemical yield and >95% purity. It binds all five somatostatin receptor subtypes and showed a binding affinity of 8.77 nM for SSTR2. In mice bearing SSTR2-positive tumors, the tracer achieved tumor-to-muscle uptake ratios greater than 5-fold, producing high-contrast PET images with no defluorination detected in vivo.
Gao, Fei; Zhang, Yunhan; Chen, MengYi; Song, ZhiHao; Dong, RuiLin; Qiu, ShanShan; Shen, Chen; Huang, XiaoYan; Geng, Hao; Cheng, Weihua; Hu, Ji ·
RPEP-08242 · 2024HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% CI of Cmax ratio was 102.9%-122.0% and AUC0-∞ ratio was 97.1%-116.9%, both within the accepted 80-125% bioequivalence range. No grade 3+ adverse events, serious adverse events, or deaths occurred. No incremental immunogenicity with the biosimilar.
Gao, Xianglei; Di, Yujing; Lv, Yuan; Luan, Yingcai; Xiong, Yang; Xu, Yuli; Li, Yusheng; Guo, Linfeng; Li, Xiaoping; Deng, Li; Zhuang, Yulei; Hou, Jie ·
RPEP-08245 · 2024Of 92 cardiovascular-related proteins measured, 43 were significantly associated with at least one of 13 subclinical cardiovascular traits. NT-proBNP (a peptide biomarker of heart stress), brachial-ankle pulse-wave velocity (arterial stiffness), and carotid plaque burden had the most protein associations.
Only three proteins — growth/differentiation factor 15, LDL receptor, and interleukin-1 receptor type 2 — were associated with all three of these key traits. Several novel associations were discovered: von Willebrand factor and galectin 4 with carotid plaque, carboxypeptidase A1 and B1 with carotid intima-media thickness, cathepsin D with arterial stiffness, and cathepsin Z, LDL receptor, neurogenic locus homolog protein 3, and TREM-like transcript 2 with NT-proBNP. Sex-specific effects were also observed for some proteins.
Garcia, Tarcyane; Petrera, Agnese; Hauck, Stefanie M; Baber, Ronny; Wirkner, Kerstin; Kirsten, Holger; Pott, Janne; Tönjes, Anke; Henger, Sylvia; Loeffler, Markus; Peters, Annette; Scholz, Markus ·
RPEP-08251 · 2024Liraglutide (0.4 mg/kg daily for 10 days) did not reduce blood sugar in streptozotocin-diabetic mice but significantly alleviated pain behavior. In the formalin test, liraglutide-treated mice in an enriched environment showed dramatically lower second-phase pain responses compared to standard housing [2.00 vs 29.00 seconds, p=0.016]. Liraglutide reduced neopterin levels (an inflammation marker) compared to untreated diabetic controls. The glutamine/glutamate ratio was significantly higher with liraglutide treatment or enriched environment compared to diabetic controls (p=0.003 and p=0.002, respectively).
Gateva, Pavlina; Hristov, Milen; Ivanova, Natasha; Vasileva, Debora; Ivanova, Alexandrina; Sabit, Zafer; Bogdanov, Todor; Apostolova, Sonia; Tzoneva, Rumiana ·
RPEP-08255 · 2024After 28 days of oral PET microplastic exposure in pigs:
- Galanin-positive neurons increased across the gut nervous system
- VIP-positive, CART-positive, and vesicular acetylcholine transporter-positive neurons decreased
- Substance P and neuronal nitric oxide synthase (nNOS) changes varied by dose and by which nerve plexus was examined
- Histological damage was dose-dependent: higher doses (1 g/day) caused more severe villus injury, cellular debris accumulation, mucus buildup, eosinophil infiltration, and hyperemia (excess blood flow)
These neurochemical changes suggest that microplastics can alter the function of the enteric nervous system — the 'second brain' that controls gut motility, secretion, and blood flow.
Gałęcka, Ismena; Całka, Jarosław ·
RPEP-08272 · 2024From 11 trials (545 intervention, 451 control participants, 12 comparisons), most anti-obesity agents improved anthropometric outcomes. Liraglutide, semaglutide, and orlistat appeared superior to placebo. Meta-analysis of exenatide vs metformin found no differences for anthropometric, hyperandrogenism, or metabolic outcomes, except metformin showed slightly lower fasting glucose (MD: 0.10 mmol/L, CI 0.02-0.17, I²=18%). Orlistat + COCP did not improve metabolic outcomes versus COCP alone (fasting insulin MD: -8.65 pmol/L, -33.55 to 16.26, I²=67%). The critical finding is the extreme paucity of evidence for a condition affecting 6-12% of reproductive-age women.
Goldberg, Alyse; Graca, Sandro; Liu, Jing; Rao, Vibhuti; Witchel, Selma Feldman; Pena, Alexia; Li, Rong; Mousa, Aya; Tay, Chau Thien; Pattuwage, Loyal; Teede, Helena; Yildiz, Bulent O; Ee, Carolyn ·
RPEP-08273 · 2024AI is transforming peptide drug discovery through three key approaches: classifier methods that predict peptide properties (antimicrobial, antitumor, etc.), predictive systems that estimate stability and bioavailability, and deep-generative models (GANs and variational autoencoders) that design entirely new peptide sequences. The authors propose a comprehensive AI-assisted pipeline from peptide design through validation. Key challenges remain: optimization of processing, careful validation of predictive models, and bridging the gap between computationally designed peptides and experimental confirmation.
Goles, Montserrat; Daza, Anamaría; Cabas-Mora, Gabriel; Sarmiento-Varón, Lindybeth; Sepúlveda-Yañez, Julieta; Anvari-Kazemabad, Hoda; Davari, Mehdi D; Uribe-Paredes, Roberto; Olivera-Nappa, Álvaro; Navarrete, Marcelo A; Medina-Ortiz, David ·
RPEP-08276 · 2024Of 19 patients with high BMI referred to a multidisciplinary liver metabolic clinic, median weight loss was 11.7 kg (range 0–33 kg). Fifteen patients were treated with a GLP-1 receptor agonist (6 with liraglutide, 8 with semaglutide, 1 with tirzepatide) and 4 received phentermine. Eight patients (42%) ultimately received a liver transplant and 4 more were waitlisted. The median time from baseline to waitlisting was approximately 5.5 months (166 days). Eighty-four percent of patients had metabolic dysfunction-associated steatohepatitis as the underlying liver condition.
Gonzalez, Humberto C; Myers, Daniel T; Venkat, Deepak ·
RPEP-08277 · 2024In 1,739 GRADE trial participants randomized to add insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin:
At 1 year:
- All treatments reduced diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001)
- Insulin glargine showed lower diabetes distress than other groups combined (-0.10, P = 0.002)
- Liraglutide showed lower diabetes distress than glimepiride or sitagliptin (-0.10, P = 0.008)
Over 3-year follow-up:
- No significant differences in total diabetes distress between groups
- Interpersonal diabetes distress remained lower for liraglutide
- No significant differences in depressive symptoms between any groups
Key conclusion: Contrary to expectations, basal insulin did NOT increase emotional distress.
Gonzalez, Jeffrey S; Bebu, Ionut; Krause-Steinrauf, Heidi; Hoogendoorn, Claire J; Crespo-Ramos, Gladys; Presley, Caroline; Naik, Aanand D; Kuo, Shihchen; Johnson, Mary L; Wexler, Deborah; Crandall, Jill P; Bantle, Anne E; Arends, Valerie; Cherrington, Andrea L ·
RPEP-08279 · 2024Chicken skin collagen hydrolysate peptide fraction F4 and its digested form (DF4) showed strong ACE-inhibitory activity with IC50 values of 188.84 and 220.03 μg/mL, respectively — approximately 2-fold more potent than the smaller peptide fraction from post-digested hydrolysate (FDH, IC50 388.57 μg/mL).
For anti-obesity effects, DF4 at 800 μg/mL reduced lipid accumulation by 83% in preadipocytes. In differentiated adipocytes, both FDH and DF4 achieved 45–60% lipid reduction regardless of concentration. Nine peptides were identified as potential ACE inhibitors in the active fractions.
González-Noriega, Julio Alfonso; Valenzuela-Melendres, Martín; Hernández-Mendoza, Adrián; Astiazarán-García, Humberto; Islava-Lagarda, Thalia; Tortoledo-Ortiz, Orlando; Huerta-Ocampo, José Ángel; de La Garza, Ana Laura; Peña-Ramos, Etna Aída ·
RPEP-08286 · 2024In a matched cohort of 3,291 veterans with diabetes and MGUS (1,097 GLP-1 RA users matched to 2,194 non-users):
- Progression to multiple myeloma: 2.6% in GLP-1 RA users vs. 5.0% in non-users
- Cumulative incidence was significantly different (P = 0.02)
- GLP-1 RA use was associated with a 55% reduction in myeloma progression (HR = 0.45, 95% CI 0.22–0.93, P = 0.03)
The analysis accounted for the competing risk of death and used a validated NLP algorithm to confirm MGUS diagnosis and progression.
Grandhi, Nikhil; Liu, Lawrence; Wang, Mei; Thomas, Theodore; Schoen, Martin; Sanfilippo, Kristen; Gao, Feng; Colditz, Graham A; Carson, Kenneth R; Janakiram, Murali; Chang, Su-Hsin ·
RPEP-08287 · 2024The collagen hydrolysate H80 (Nextida GC) demonstrated GLP-1-mediated metabolic improvements:
**In mice:**
- Blood glucose response reduced by 25% in lean and 36% in prediabetic mice at 4 g/kg
- Plasma active GLP-1 increased by 217% in lean and 860% in prediabetic mice
- Gastric emptying slowed by 60% after 21 days of supplementation
- Plasma insulin increased by 166% after 35 days of supplementation
**In humans (proof of concept):**
- A 5 g oral dose of H80 reduced postprandial glucose response in healthy, normoglycemic, and prediabetic participants
The mechanism appears to work through stimulating natural GLP-1 secretion from intestinal L-cells, mimicking the physiological pathway that GLP-1 receptor agonist drugs target pharmacologically.
Grasset, Estelle; Briand, François; Virgilio, Nicolina; Schön, Christiane; Wilhelm, Manfred; Cudennec, Benoit; Ravallec, Rozenn; Aboubacar, Hairati; Vleminckx, Sara; Prawitt, Janne; Sulpice, Thierry; Gevaert, Elien ·
RPEP-08290 · 2024In women with idiopathic intracranial hypertension (IIH), exenatide (a GLP-1 receptor agonist) did not compromise cognition over 12 weeks compared to placebo. Patients treated with exenatide showed significant improvements in fluid intelligence (T-score 38.4→52.9, p=0.0005), processing speed (43.7→58.4, p=0.0058), and episodic memory (49.4→62.1, p=0.0315). Baseline cognitive impairment was confirmed in fluid intelligence, attention, and executive function (all T-scores well below population mean of 50).
Grech, Olivia; Mitchell, James L; Lyons, Hannah S; Yiangou, Andreas; Thaller, Mark; Tsermoulas, Georgios; Brock, Kristian; Mollan, Susan P; Sinclair, Alexandra J ·
RPEP-08295 · 2024Among 11 neuroendocrine tumor patients who received repeat PRRT after disease progression:
Efficacy after PRRT2 (at first restaging, 3-6 months):
- Partial response: 18.2% (2/11)
- Stable disease: 36.4% (4/11)
- Progressive disease: 27.3% (3/11)
- Died before restaging: 18.2% (2/11)
- Overall disease control rate: 54.5% (6/11)
Progression-free survival:
- PRRT1: 25.4 months median PFS
- PRRT2: 13.1 months median PFS
- Difference statistically significant (P = 0.0001)
Safety: No significant difference in hematological or renal toxicity rates between PRRT1 and PRRT2.
Grewal, Udhayvir S; Loeffler, Bradley T; Paschke, Alexander; Dillon, Joseph S; Chandrasekharan, Chandrikha ·
RPEP-08296 · 2024Among 2,168 patients with T2D and baseline HbA1c ≥7% who initiated once-weekly semaglutide 1.0 mg, the mean HbA1c reduction was 1.2% (p<0.001). Similar reductions were observed in the persistent patient subgroup (those with at least 90 days of continuous treatment).
The patient population was notably medically complex: patients were taking an average of 13.5 different medication classes, and comorbidity rates were high — lipid metabolism disorder (90.8%), hypertension (86.6%), diabetes with complications (86.8%), and other metabolic disorders (72.5%). Despite this burden of disease, semaglutide consistently lowered blood sugar, confirming its effectiveness in the most challenging real-world patient populations.
Gronroos, Noelle N; Swift, Caroline; Frazer, Monica S; Sargent, Andrew; Leszko, Michael; Buysman, Erin; Alvarez, Sara; Dunn, Tyler J; Noone, Josh ·
RPEP-08297 · 2024Starting from previously identified 13-amino acid cyclic peptides, the researchers used structure-based design to create truncated, electrically neutral versions that maintained full ability to disrupt the PCSK9/LDL-receptor protein-protein interaction in both biochemical and cellular assays.
The original larger peptides required charged chemical groups to function and lacked oral bioavailability in rodents — a major barrier to pill development. The new truncated versions eliminated this charge requirement.
In parallel, mRNA-peptide display screening identified novel 8- and 9-amino acid compounds that bind the same induced-fit pocket on PCSK9 but in a structurally distinct manner. Although these shorter peptides were not functionally active on their own, they demonstrate that smaller molecules can access this binding site, providing additional starting points for further optimization toward true small-molecule oral agents.
Grosche, Philipp; Flyer, Alec N; Gattlen, Raphael; Xu, Mei; Golosov, Andrei A; Vera, Victoria; Pickett, Stephanie; Brousseau, Margaret E; Chopra, Rajiv; Clairmont, Kevin B; Koch, Alexander; Liu, Eugene; Reid, Patrick; Perry, Lauren; Yang, Lihua; Yang, Qing; Monovich, Lauren G ·
RPEP-08301 · 2024From 16,123 venom proteins, the APEX deep learning model generated 40,626,260 venom-encrypted peptides (VEPs) and identified 386 candidates structurally and functionally distinct from known antimicrobial peptides. These VEPs had high net charge and elevated hydrophobicity — properties that enable bacterial membrane disruption.
Of 58 VEPs selected for experimental validation, 53 (91%) displayed potent antimicrobial activity. Structural studies showed the peptides adopt α-helical conformations in membrane-mimicking environments. Mechanistic assays confirmed they work by depolarizing bacterial membranes. In vivo, lead VEPs significantly reduced A. baumannii bacterial burdens in a mouse infection model without notable toxicity.
Guan, Changge; Torres, Marcelo D T; Li, Sufen; de la Fuente-Nunez, Cesar ·
RPEP-08306 · 2024Among 209,354 adverse drug reports in FAERS (2005-2023), 5,378 involved psychiatric disorders and 383 were classified as serious. After pharmacovigilance unmasking, 271 cases implicated individual GLP-1 RAs:
- Liraglutide: n=90, ROR=1.64
- Semaglutide: n=61, ROR=2.03
- Exenatide: n=67, ROR=0.80
- Dulaglutide: n=45, ROR=0.84
- Tirzepatide: n=5, ROR=1.76
42 deaths were recorded including 13 completed suicides. Suicidal ideation was reported for 6 of 7 GLP-1 RAs (all except lixisenatide). Critically, metformin had a greater association with these adverse events than GLP-1 drugs, while orlistat did not. No causal link could be established.
Guirguis, A; Chiappini, S; Papanti P, G D; Vickers-Smith, R; Harris, D; Corkery, J M; Arillotta, D; Floresta, G; Martinotti, G; Schifano, F ·
RPEP-08314 · 2024Liraglutide, a GLP-1 receptor agonist, protected mice from sepsis-induced acute lung injury (ALI) by restoring pulmonary surfactant production and inhibiting excessive autophagy. Treated mice survived longer, had less lung inflammation, less pulmonary edema (lower wet/dry weight ratio), and less cell death compared to untreated ALI mice. In cell culture, liraglutide reversed the damage caused by bacterial toxins (LPS) and restored expression of surfactant proteins SP-A and SP-B. The protective effects were blocked by rapamycin (an autophagy activator), confirming that liraglutide works by inhibiting autophagy.
Guo, Junping; Zhang, Xiao; Pan, Ran; Zheng, Yueliang; Chen, Wei; Wang, Lijun · Animal Study
RPEP-08315 · 2024The peptide CI5, isolated from Cinobufacini injection, demonstrated significant analgesic and anti-inflammatory effects in multiple mouse models. It relieved pain in the acetic acid writhing test and formalin inflammatory pain model, and prevented carrageenan-induced paw edema.
Mechanistically, CI5 reduced levels of key inflammatory markers (IL-6, TNF-α, IL-1β, and PGE2). LC-MS/MS analysis revealed that CI5 exerts its effects by binding to the Rac-2 protein, which sits upstream of the ERK1/2/COX-2 inflammatory signaling axis — the same pathway targeted by common NSAIDs like ibuprofen.
Guo, Li; Zhang, Sai; Zhang, Cong; Ren, Shuang; Zhou, Zihan; Wang, Fengyuan; Wang, Yuexuan; Chen, Qiqi; Wang, Yubing; Lee, Wen-Hui; Zhu, Kui; Qin, Di; Gao, Yuanyuan; Sun, Tongyi ·
RPEP-08321 · 2024Four studies (3 RCTs + 1 observational study) examining semaglutide in heart failure patients found statistically significant improvements in:
- Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (P<0.001) — measuring quality of life and symptom burden
- Body weight reduction (P<0.001)
- Six-minute walk distance (P<0.001) — measuring exercise capacity
- C-reactive protein (CRP) levels (P<0.001) — measuring systemic inflammation
- Major adverse cardiac events: HR = 0.76 (95% CI: 0.62–0.92) — a 24% risk reduction
Adverse effects were observed but were not significantly worse than placebo.
Gupta, Nishtha; Uwawah, Tesingin D; Singh, Kamaldeep; Madan, Hritik; Kumar, Siddharth; Midha, Bharat; Soni, Kriti; Singh, Aparjit; Bhogal, Amandeep; Jain, Arpit ·
RPEP-08323 · 2024Among 1,165 SARS-CoV-2 hospitalized patients without pre-existing dry eye:
- 167 patients (14.3%) developed dry eye disease within 6 months of discharge
- Metoclopramide: strongest association, OR 13.413 (p<0.001), >50% incidence in affected patients
- Laxatives: lactulose OR 1.939 (p=0.016), polyethylene glycol OR 2.094 (p=0.015)
- Omeprazole: protective, OR 0.332 (p<0.001) — 67% risk reduction
- Polypharmacy increased dry eye odds: OR 1.629 (p=0.015)
- Age, gender, and vaccination status were not significant
Vasoactive intestinal peptide (VIP) is proposed as the pathophysiological link between gut and lacrimal gland function, connecting GI medication effects to dry eye outcomes.
Gushansky, Konstantin Y; Tuuminen, Raimo ·
RPEP-08329 · 2024Neurokinin A (NKA), a tachykinin neuropeptide, directly interacts with Alzheimer's Aβ1-42 peptide and modulates its amyloid aggregation cascade. A phenylalanine residue in NKA's FXGLM signature motif was critical for this interaction (demonstrated by Phe-to-Trp substitution). Cellular experiments showed that the NKA-Aβ interaction decreased Aβ peptide toxicity, suggesting NKA may have a protective role against amyloid-driven cell damage.
Habibnia, Mohsen; Catalina-Hernandez, Eric; Lopez-Martin, Mario; Masnou-Sanchez, David; Peralvarez-Marin, Alex ·
RPEP-08330 · 2024Extensive laboratory testing of 26 follow-on (generic/compounded) GLP-1 products — 16 injectable semaglutide, 8 oral semaglutide, and 2 injectable liraglutide — revealed significant quality concerns compared to brand-name originator products.
Key problems found: follow-on injectable semaglutide products contained new impurities including high molecular weight proteins, trace metals, anions, counterions, and residual solvents. Several oral semaglutide follow-ons had markedly less semaglutide than their labels claimed and showed different drug release profiles that could reduce how much drug actually gets absorbed. Some follow-on products contained neoepitopes — protein fragments not found in originators — that could trigger unwanted immune reactions. Liraglutide follow-ons showed increased tendency to form fibrils (protein aggregates), indicating reduced physical stability.
Hach, Morten; Engelund, Dorthe Kot; Mysling, Simon; Mogensen, Jesper Emil; Schelde, Ole; Haselmann, Kim F; Lamberth, Kasper; Vilhelmsen, Thomas Kvistgaard; Malmstrøm, Joan; Højlys-Larsen, Kim Bonde; Rasmussen, Tina Secher; Borch-Jensen, Jonas; Mortensen, Rasmus Worm; Jensen, Thomas Marker Thams; Kesting, Julie Regitze; Catarig, Andrei-Mircea; Asgreen, Désirée J; Christensen, Leif; Staby, Arne · Laboratory Analysis
RPEP-08332 · 2024Dulaglutide treatment produced significant reductions in two key biomarkers of atherosclerotic plaque instability: pentraxin 3 (PTX3) and matrix metalloproteinase-9 (MMP-9). Both markers are associated with plaque vulnerability — the likelihood that a fatty deposit in an artery will rupture and cause a heart attack or stroke.
The study also documented significant improvements in anthropometric measurements, blood pressure, fasting glucose, and HbA1c levels (median baseline 8.8%), demonstrating that dulaglutide's cardiovascular benefits may operate through multiple pathways simultaneously.
Hachuła, Marcin; Kosowski, Michał; Basiak, Marcin; Okopień, Bogusław ·
RPEP-08333 · 2024Salep extract at 160 and 320 mg/kg caused significant weight loss in rats over 29 days. The extract shifted the balance of appetite-regulating peptides in favor of satiety:
Increased: leptin, adiponectin, AgRP, obestatin, CCK, chemerin, and total antioxidants.
Decreased: ghrelin, omentin, resistin, NPY, amylin, orexin-A, epinephrine, and MDA (oxidative stress marker).
Lipid profiles also improved. The simultaneous reduction of multiple appetite-stimulating peptides (ghrelin, NPY, orexin-A) combined with elevation of satiety signals (CCK, obestatin, leptin) suggests a broad anti-obesity mechanism affecting both central and peripheral appetite regulation.
Haghshenas, H; Molayem, M; Shafiei Jahromi, N; Kargar Jahromi, H; Dehghani, M; Ebrahimi, B; Moazeni, R; Rezaeian, S; Shaterian, N; Daniali, S ·
RPEP-08336 · 2024Head-to-head clinical studies showed that GLP-1 receptor agonists outperform conventional antidiabetic medicines in both glycemic management and weight reduction. Cardiovascular outcome studies found that several drugs in this class reduce the frequency of major adverse cardiovascular events.
The medications also show promise for non-alcoholic fatty liver disease (NAFLD). However, the high cost of these drugs creates significant barriers to access and equitable healthcare. Current research is focused on expanding therapeutic applications and developing oral formulations with greater potency and bioavailability.
Hamed, Khalid; Alosaimi, Mohammed N; Ali, Bashaer A; Alghamdi, Atheer; Alkhashi, Taif; Alkhaldi, Salman S; Altowarqi, Nawaf A; Alzahrani, Hayat; Alshehri, Abdullah M; Alkhaldi, Rami K; Alqahtani, Khalid W; Alharbi, Nehal H; Alhulayfi, Hanan F; Sharifi, Shuruq Y; Dighriri, Ibrahim M ·
RPEP-08356 · 2024Mining the FDA's adverse event database (FAERS) revealed that semaglutide, liraglutide, and exenatide have the highest rates of metabolic and nutritional adverse events among GLP-1 drugs. Semaglutide had the strongest signal (ROR 3.34), followed by liraglutide (ROR 2.78) and exenatide (ROR 2.15).
Dehydration emerged as the most common serious metabolic side effect across multiple GLP-1 drugs: it accounted for 25.1% of serious metabolic adverse events for semaglutide, 32.9% for tirzepatide, 23.9% for liraglutide, and 20.9% for dulaglutide. Dulaglutide had the most total adverse event signal types (22), followed by semaglutide (20) and liraglutide (16).
He, Long; Li, Qiuyu; Yang, Yongfeng; Li, Jiahao; Luo, Wei; Huang, Yilan; Zhong, Xiaoyan · Pharmacovigilance / Database Analysis
RPEP-08357 · 2024The BSA@LIR-PMF nanoparticles achieved a drug loading rate of 7.96% and encapsulation efficiency of 85.56%, with approximately 77% cumulative drug release over 24 hours. The nanoparticles were spherical, uniform in size, and maintained stable platelet membrane protein structure.
In functional testing, the nanoparticles effectively inhibited abnormal cell proliferation and migration triggered by oxidized LDL (ox-LDL), reduced reactive oxygen species (ROS) levels and lactate concentrations, and enhanced ATP levels by improving oxidative phosphorylation. In animal models, BSA@LIR-PMF significantly inhibited diabetes-induced atherosclerosis and reduced lipid deposition in the aortas.
He, Mingping; Fang, Ming; Fan, Limin; Maimaitijiang, Alimujiang ·
RPEP-08361 · 2024GLP-1 receptor agonists have emerged as an effective weight loss option for morbidly obese patients with hip or knee osteoarthritis who need joint replacement surgery. These patients typically present earlier in life, have more severe symptoms, and experience worse surgical outcomes after total hip or knee arthroplasty.
Beyond weight loss, GLP-1 agonists may have anti-inflammatory and disease-modifying effects on osteoarthritis itself. The review covers single GLP-1 agonists, dual GLP-1/GIP agonists, and triple GLP-1/GIP/glucagon agonists in development.
However, a critical perioperative concern is GLP-1-related delayed gastric emptying, which affects anesthesia timing for elective joint replacement surgery. Surgeons must account for this when planning procedures in patients taking these medications.
Heckmann, Nathanael D; Palmer, Ryan; Mayfield, Cory K; Gucev, Gligor; Lieberman, Jay R; Hong, Kurt · Review
RPEP-08363 · 2024The warehouse-based immunopeptidome-guided vaccine design was feasible for all 26 CLL patients, proving the personalized approach works at a practical level. Vaccination was well-tolerated, with local injection site reactions being the most common adverse event. However, only a few patients showed vaccine-induced T cell responses, attributed to immunosuppression from prior immuno-chemotherapy and the lack of a sufficiently potent adjuvant.
A follow-up trial (NCT04688385) is now combining this warehouse approach with a more potent adjuvant and BTK inhibitor therapies that support T cell function, addressing the key limitations identified.
Heitmann, Jonas S; Jung, Susanne; Wacker, Marcel; Maringer, Yacine; Nelde, Annika; Bauer, Jens; Denk, Monika; Hoenisch-Gravel, Naomi; Richter, Marion; Oezbek, Melek T; Dubbelaar, Marissa L; Bilich, Tatjana; Pumptow, Marina; Martus, Peter; Illerhaus, Gerald; Denzlinger, Claudio; Steinbach, Francesca; Aulitzky, Walter-Erich; Müller, Martin R; Dörfel, Daniela; Rammensee, Hans-Georg; Salih, Helmut R; Walz, Juliane S ·
RPEP-08374 · 2024Of 91 previously identified tumor-specific antigens from ovarian cancer, 48 were selected for immunogenicity testing. When dendritic cells were pulsed with synthetic peptide versions of these antigens, they presented them at high levels on their surface. These peptide-loaded dendritic cells successfully expanded sizeable populations of CD8 T cells from healthy donors, confirming that the immune system can recognize and respond to these non-mutated cancer antigens.
The abundance of antigen presentation correlated with predicted HLA binding affinity, suggesting that computational tools can help predict which antigens will be most immunogenic.
Hesnard, Leslie; Thériault, Catherine; Cahuzac, Maxime; Durette, Chantal; Vincent, Krystel; Hardy, Marie-Pierre; Lanoix, Joël; Lavallée, Gabriel Ouellet; Humeau, Juliette; Thibault, Pierre; Perreault, Claude ·
RPEP-08375 · 2024The KISS1/PDYN (kisspeptin/prodynorphin) ratio was significantly higher in PCOS women compared to controls (p=0.02). Prodynorphin expression was significantly lower in the PCOS group (p<0.001). The positive correlation between KISS1 expression and the KISS1/PDYN ratio was much stronger in PCOS women (R=0.93, p<0.001) than controls (R=0.66, p<0.001).
The authors conclude that diminished dynorphin expression — not elevated kisspeptin alone — drives the increased ratio, and that this imbalance is highly specific to PCOS.
Hestiantoro, Andon; Noor Al Maghfira, Rachellina; Fathmasari, Ratna; Rahmala Febri, Ririn; Ongko Joyo, Ericko; Muharam, Raden; Pratama, Gita; Bowolaksono, Anom ·
RPEP-08377 · 2024In 69 patients with both heart failure and renal anemia, HIF-PH inhibitors raised hemoglobin levels that had been declining during the prior 6 months without treatment. Starting hemoglobin was 9.2 g/dL after a decline from 10.5 g/dL in the pre-treatment period. Beyond correcting anemia, the treatment was associated with improvements in BNP levels (a peptide biomarker indicating heart failure severity), kidney function, and markers of systemic inflammation.
This suggests that treating renal anemia with HIF-PH inhibitors may have benefits beyond blood counts — potentially improving the interconnected cycle of heart failure, kidney disease, and anemia known as cardiorenal anemia syndrome.
Hida, Yuki; Imamura, Teruhiko; Kinugawa, Koichiro · Observational Study
RPEP-08385 · 2024In a propensity score-matched cohort using South Korean national health data (2010-2022), 12,489 patients initiating SGLT2 inhibitors (dapagliflozin or empagliflozin) and 1,075 patients initiating dulaglutide were compared. Over a median follow-up of 4.4 years:
- Dementia events: 69 in the SGLT2 inhibitor group vs. 43 in the dulaglutide group
- Risk difference: -0.91 percentage points (95% CI: -2.45 to 0.63) — not statistically significant
- Risk ratio: 0.81 (95% CI: 0.56 to 1.16) — not statistically significant
The data were compatible with dementia risk being anywhere from 2.5 percentage points lower to 0.6 percentage points higher for SGLT2 inhibitors compared to dulaglutide.
Hong, Bin; Bea, Sungho; Ko, Hwa Yeon; Kim, Woo Jung; Cho, Young Min; Shin, Ju-Young ·
RPEP-08386 · 2024In preclinical models (cell and animal studies), multiple GLP-1 receptor agonists demonstrated significant neuroprotective effects through several mechanisms: reducing neuroinflammation, enhancing autophagy (cellular cleanup), improving mitochondrial function, and preventing abnormal phosphorylation of disease-related proteins (tau in AD, α-synuclein in PD). These effects translated to improvements in cognitive and motor function in animal models.
However, clinical trials investigating GLP-1RAs in AD, PD, mild cognitive impairment, psychiatric disorders, and diabetes have produced mixed results. Some trials showed cognitive or motor benefits while others did not demonstrate significant improvements over placebo. The review proposes that trial design issues — including patient selection, treatment duration, and outcome measures — may partly explain the inconsistent results.
Hong, Chien-Tai; Chen, Jia-Hung; Hu, Chaur-Jong ·
RPEP-08392 · 2024Olanzapine induced hyperphagia, weight gain, and increased triglycerides and HDL cholesterol in rats. Dulaglutide alone modestly decreased food intake but did not prevent weight gain or reverse olanzapine-induced lipid changes. Food restriction alone affected the obesity phenotype but not serum markers. However, the combination of dulaglutide + food restriction produced synergistic effects: weight loss, decreased feed efficiency, and lower total and HDL cholesterol.
The dramatic synergy between GLP-1RA treatment and dietary restriction suggests these interventions work through complementary mechanisms that amplify each other's benefits in the context of antipsychotic-induced metabolic dysfunction.
Horska, Katerina; Kucera, Jan; Drazanova, Eva; Kuzminova, Gabriela; Amchova, Petra; Hrickova, Maria; Ruda-Kucerova, Jana; Skrede, Silje ·
RPEP-08400 · 2024Compared with GLP-1 receptor agonists, empagliflozin was associated with:
- Similar risk of MI or stroke: HR 0.99 (95% CI: 0.92-1.07)
- 50% lower risk of heart failure hospitalization: HR 0.50 (0.44-0.56)
- 10% lower risk of MACE: HR 0.90 (0.82-0.99)
- 23% lower risk of CV mortality or HHF composite: HR 0.77 (0.69-0.86)
- 25% lower risk of progression to ESKD in CKD stage 3-4 patients: HR 0.75 (0.60-0.94)
Absolute risk reductions were larger in older patients and those with baseline ASCVD or heart failure. Benefits did not differ by sex.
Htoo, Phyo T; Tesfaye, Helen; Schneeweiss, Sebastian; Wexler, Deborah J; Everett, Brendan M; Glynn, Robert J; Schmedt, Niklas; Koeneman, Lisette; Déruaz-Luyet, Anouk; Paik, Julie M; Patorno, Elisabetta ·
RPEP-08405 · 2024Peptide supplementation significantly extended the lifespan of C. elegans, reducing mortality risk by 46% (hazard ratio = 0.54, 95% CI: 0.47-0.62, p<0.05). Beyond living longer, peptide-treated worms also showed signs of healthier aging: pharyngeal pumping rate increased significantly (SMD = 1.64), bending frequency improved (SMD = 1.67), and lipofuscin accumulation — a marker of cellular aging — decreased dramatically (SMD = -4.48).
Subgroup analysis revealed that doses of 0.1-1 mg/mL showed the best anti-aging effects (HR = 0.50, 95% CI: 0.38-0.65), suggesting an optimal dosing range for peptide-based lifespan extension.
Huang, Chao; Zhu, Ling; Zhang, Hui; Liu, Tongtong; Wang, Li; Wu, Gangcheng ·
RPEP-08407 · 2024The MLSV system (DMP nanoparticles loaded with tumor cell lysate and modified with TAT-iRGD cell-penetrating peptide) achieved several key outcomes when loaded with Bim-encoding mRNA:
Delivery: 68.6% transfection rate in B16 melanoma cells via caveolin-mediated endocytosis. Nanoparticle size was 191.4 nm with +47.8 mV surface charge.
Immune activation: Induced dendritic cell maturation with increased CD80, CD86, and MHC-II expression both in vitro and in vivo.
Anti-tumor efficacy: 87.3% growth inhibition in vitro; 78.7% tumor growth inhibition in subcutaneous B16 melanoma model; 63.3% inhibition in pulmonary metastatic B16 model in vivo.
Huang, Jing; Wang, Kaiyu; Wu, Shan; Zhang, Jin; Chen, Xiayu; Lei, Sibei; Wu, Jieping; Men, Ke; Duan, Xingmei ·
RPEP-08408 · 2024Liraglutide protects against diabetic kidney disease by suppressing the TLR4/MyD88/NF-κB inflammatory signaling pathway. In cell culture, liraglutide reduced high-glucose-induced activation of this pathway, decreased inflammatory factors, and lowered extracellular matrix protein levels in kidney mesangial cells. When TLR4 was activated by LPS or overexpressed, it eliminated liraglutide's protective effects, confirming the pathway dependency. In diabetic mice, 8 weeks of liraglutide treatment significantly improved kidney damage, reduced inflammation and fibrosis. TLR4 knockout diabetic mice showed similar improvements, and liraglutide provided additional benefit even in TLR4 knockout mice.
Huang, Linjing; Lin, Tingting; Shi, Meizhen; Wu, Peiwen ·
RPEP-08410 · 2024The review traces the development of three major classes of gut hormone multi-agonists: dual GLP-1/glucagon receptor agonists (first discovered 2009), dual GLP-1/GIP receptor agonists (first described 2013), and triple GLP-1/GIP/glucagon receptor agonists (first designed 2015).
Tirzepatide, a dual GLP-1/GIP agonist approved by the FDA for type 2 diabetes, outperformed both basal insulin and selective GLP-1 receptor agonists in HbA1c reduction. In non-diabetic individuals with obesity, tirzepatide achieved up to 22.5% weight loss — results comparable to certain bariatric surgeries.
Huang, Xianxian; Liu, Jing; Peng, Guangquan; Lu, Mingyue; Zhou, Zhongbo; Jiang, Neng; Yan, Zhiming ·
RPEP-08411 · 2024Nanoparticles (~100 nm) coated with exendin-4 (a GLP-1 peptide) and loaded with deferoxamine (an iron chelator) successfully crossed the blood-brain barrier and reached the brain in a Parkinson's disease mouse model. The Ex-4@DFO NPs achieved synergistic neuroprotection through two mechanisms: iron chelation (removing toxic iron accumulation) and GLP-1 receptor-mediated anti-inflammatory effects.
In MPTP-induced PD mice, the nanoparticles significantly reduced dopaminergic neuron loss and neuroinflammation in the substantia nigra, and improved mobility deficits. In vitro, the particles protected neuronal mitochondria and reduced inflammatory factor release from microglial cells.
Huang, Yiming; Wang, Xinran; Li, Wenjing; Yue, Feng; Wang, Miao; Zhou, Feifan ·